Alzheimer Disease for Step 1: Plaques, Tangles & Dementias

Creator: Progress Note
Published: 2026-08-27
Keywords: Alzheimer's disease, alzheimer disease usmle, amyloid plaques neurofibrillary tangles, apoe e4, dementia types step 1, lewy body dementia, frontotemporal dementia pick bodies, normal pressure hydrocephalus triad, delirium vs dementia, donepezil memantine

bolt The 60-second version

check_circleAlzheimer disease is the most common dementia: gradual memory loss first, then language, visuospatial, and executive decline.
check_circlePathology: extracellular amyloid-β plaques, intracellular neurofibrillary tangles of hyperphosphorylated tau, hippocampal and cortical atrophy, and loss of cholinergic neurons (nucleus basalis of Meynert).
check_circleGenetics: APOE ε4 raises late-onset risk (ε2 is protective); APP (chromosome 21), PSEN1, and PSEN2 cause early-onset disease. Down syndrome brings early Alzheimer disease.
check_circleTreatment: cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine (NMDA antagonist); anti-amyloid antibodies for early disease.
check_circleOther dementias: Lewy body (hallucinations, fluctuations, parkinsonism), frontotemporal (personality change, earlier onset), vascular (stepwise), normal pressure hydrocephalus (gait, incontinence, confusion), prion disease (rapid with myoclonus).
check_circleAlways rule out reversible causes: vitamin B12 deficiency, hypothyroidism, syphilis, depression, and medications.

target What you'll be able to do · aligned to USMLE Step 1 · Nervous System

NEURODistinguish delirium from dementia.
PATHDescribe the pathology and genetics of Alzheimer disease.
NEURODifferentiate Lewy body, frontotemporal, vascular, NPH, and prion dementia.
PHARMIdentify dementia treatments and reversible causes.

How dementia is tested on Step 1

First separate dementia from delirium.

Delirium vs dementia. People with dementia are more prone to delirium, and the two often coexist.

Alzheimer disease pathology and genetics

Two protein abnormalities define the disease.

Amyloid plaques: amyloid-β made when APP is cleaved by β- and γ-secretase; deposits can also involve vessel walls (cerebral amyloid angiopathy, causing lobar hemorrhages).
Neurofibrillary tangles: hyperphosphorylated tau; their number correlates with the degree of dementia.
Atrophy: widened sulci and enlarged ventricles, worst in the hippocampus and temporal and parietal lobes.
Genes: APOE ε4 (risk), APP on chromosome 21, presenilins (PSEN1, PSEN2) in early-onset familial cases.

Other dementias

The first symptom and the speed of decline point to the type.

Dementia types. Normal pressure hydrocephalus is a treatable cause: gait often improves after removing CSF.

Treatment and reversible causes

Screen for treatable causes before labeling dementia degenerative.

Approach	Examples	Notes
Cholinesterase inhibitors	Donepezil, rivastigmine, galantamine	Raise ACh; GI upset, bradycardia
NMDA antagonist	Memantine	Moderate to severe disease; blocks excitotoxicity
Anti-amyloid antibodies	Lecanemab, donanemab	Early disease; risk of amyloid-related imaging abnormalities (brain edema, microbleeds)
Reversible causes to test	B12, TSH, syphilis, depression, medications	Anticholinergic and sedative drugs worsen cognition

Depression can mimic dementia in older adults ("pseudodementia").

Worked example

Use the distinctive features.

functions Worked example — hallucinations and stiffness

A 74-year-old has a year of memory decline with days of near-normal alertness alternating with confusion. They describe seeing small children in the room. Mild rigidity and bradykinesia are present. After a dose of haloperidol for agitation, they become severely rigid. What is the diagnosis?

Fluctuating cognition and well-formed visual hallucinations are core features of Lewy body dementia.
Parkinsonism supports it.
Severe sensitivity to D2-blocking antipsychotics is classic.
Pathology shows cortical Lewy bodies made of α-synuclein.

Answer. Dementia with Lewy bodies; avoid typical antipsychotics.

Next in the roadmap

Demyelinating & Neuromuscular

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Try it now

2 real questions on Alzheimer Disease & Dementia

Straight from the Progress Note question bank, each with a cited explanation. No account needed.

A 72-year-old woman presents with resting tremor, rigidity, and bradykinesia. A midbrain biopsy shows loss of pigmented neurons in the substantia nigra with intracellular eosinophilic inclusions composed of alpha-synuclein. Which diagnosis is most consistent with these findings?

Image for question 1 — Jensflorian, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons

A brain biopsy demonstrates extracellular beta-amyloid plaques and intracellular neurofibrillary tangles. Which disease is most consistent with these findings?

Image for question 2 — Mikael Häggström, M.D., CC0, via Wikimedia Commons

Frequently asked questions

What are neurofibrillary tangles made of?expand_more

Hyperphosphorylated tau protein.

Why do people with Down syndrome develop Alzheimer disease early?expand_more

The APP gene is on chromosome 21, so an extra copy increases amyloid production.

What is the triad of normal pressure hydrocephalus?expand_more

Gait disturbance, urinary incontinence, and confusion.

How does memantine work?expand_more

It blocks NMDA receptors, reducing glutamate excitotoxicity.

References & further reading

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